The invention relates to agents or galenic formulations for the treatment, prophylaxis and metaphylaxis of functional disorders of the skin as a result of external influences and/or as a result of other diseases. It has its preferred fields of application in human and veterinary medicine in the treatment, prophylaxis or metaphylaxis of skin damage caused by environmental factors, especially caused by the effect of energy-rich radiation or by the action of toxic oxygen species, dry skin conditions, ageing of the skin or photosensitivity of the skin which manifest themselves as erythematous, inflammatory, allergic or autoimmune reactive symptoms. Furthermore, the invention relates to different galenic preparations which serve skin care from the cosmetic and/or dermatological viewpoint.
In galenic formulations, which are intended to protect against UV light, predominantly light absorbers are contained. In order to lessen the epidermal damage caused by the radiation, on the one hand substances are used which absorb the UV-B range of the sunlight between 280 and 320 nm. On the other hand, substances are incorporated which can absorb UV-A light in the range between 320 and 400 nm. Thus possible dermal damage which relates to the elastic fibres and the collagen stroma and the ageing of the skin visibly connected therewith, can be avoided. A further possible way of averting impairment from UV light, consists in the application of micronised particles (physical protection from light) which reflect the light on the skin surface.
The UV radiation leads to photochemical reactions, the photochemical reaction products, in particular toxic oxygen products, having a negative effect on the skin""s metabolism. The toxic oxygen products derived from oxygen are for example energy-activated oxygen atoms. A representative of this reactive species is singlet oxygen which is considerably more reactive than the normal diradical triplet oxygen. Additional radical derivatives are superoxide anion and hydroxyl radical. As intermediates in the conversion of the superoxide anion into the hydroxyl radical, hydrogen peroxide occurs; in further reactions also harmful epoxides occur. These toxic oxygen species and the reaction products with the skin components also occur in the course of the normal metabolism to a limited extent. On exposure to energy-rich radiation, they are formed to an excess and are the cause of pathological skin conditions and accelerated skin ageing (xe2x80x9cSkin Diseases Associated with Oxidative Injuryxe2x80x9d. In xe2x80x9cOxidative Stress in Dermatologyxe2x80x9d, Marcel Decker Inc. N.Y., Basle, Hong Kong ed. J. Fuchs and Lester Packer).
In order to neutralise toxic oxygen products formed and in order to control oxidation processes, substances are used which trap and extinguish radicals (radical scavengers) and/or which act as antioxidants. Such radical scavengers are described in great number in the literature. Often they are also described as primary antioxidants because they inhibit oxidative processes by terminating the radical chain reaction. The most well-known primary antioxidants used in topical formulations are for example sesamol, gallic acid, flavones or flavonoids (EP OS 595 694, DE 197 42 025A, DE 197 39 044, DE 196 51 428, DE OS 586 303 and EP OS 595 695). In DE 197 42 025A, flavones and flavonoids are quoted as active substances acting against the age-related cross-linking of dermal proteins which is seen as the cause of age spots.
What is disadvantageous about all these compounds is that they are either of synthetic origin or have to be extracted from plants and animals. They are not physiological in the concentration in which they are applied topically and in their application there is no guarantee that they will not be damaging to health, in particular in their long-term effect. Tocopherol or vitamin E (U.S. Pat. Nos. 4,144,325 and 4,248,861), which particularly inhibits the autooxidation of fats, occurs in human organisms. Since vitamin E is involved in a number of metabolic processes, an over-supply of same is not without risks.
Another substance which occurs in human organisms and can be manufactured by bioengineering with the aid of microorganisms, is hyaluronic acid. This is a particularly safe biopolymer which occurs in a mammal in a structure-forming manner in correspondingly large amounts. As a hydrocolloid it is in a position to bind a lot of water.
Hydrocolloid substances are used in preparations for external application in order to exploit the water-binding capacity of the compounds. In particular the highly biocompatible hyaluronic acid is present in many formulations as a water-binding substance. (U.S. Pat. Nos. 5,882,664, 5,391,373, 5,254,331, 5,087,446). In addition to tannins or catechins as oxygen radical scavengers to remove active oxygen and free radicals, hyaluronic acid is quoted in JP-9241637 in a formulation as a water-binding substance. In U.S. Pat. No. 5,571,503 hyaluronic acid is proposed besides esters of vitamin E, retinol and vitamin C in sun creams and in U.S. Pat. Nos. 5,886,142 and 5,942,245 in addition to antioxidants such as superoxide dismutase, cysteine and vitamin E to improve the hydration of the skin.
Hyaluronic acid is credited, in addition to its water-binding property, with properties of wound healing, encouraging the formation of vessels and improving penetration. In topical compositions according to DE 198 05 827A, hyaluronic acid effects protection of the skin against irritations. In U.S. Pat. No. 5,728,391, in an agent for treating skin disease, hyaluronic acid with a relative molar mass between 800 and 4,000 D is proposed.
In particular low-molecular hyaluronic acid fractions, which are produced for example from high-molecular hyaluronic acid of animal origin through splitting by means of ultrasound in the presence of hypochlorite (EP 0 944 007) have properties of healing wounds or encouraging the formation of vessels. In U.S. Pat. No. 4,303,676, hyaluronic acid mixtures are proposed between a hyaluronic acid fraction having relative molar masses of 10 to 200 kD and a second fraction with 1,000 and 4,5000 kD from cockscombs.
The object of the present invention therefore is to propose an agent for protecting the skin which in particular is biocompatible and is suitable for long-term application in human and veterinary medicine. The agent should be suitable for the treatment and/or the prophylaxis of traumatic symptoms and inflammations and ageing processes, due to environmental factors and/or as the consequence of other illnesses, including the effect of energy-rich radiation or of damage caused by the action of toxic oxygen products, without side effects occurring. Furthermore it is an object of the present invention that the agent can be used to care for or protect the skin from a cosmetic and/or dermatological viewpoint.
This object preferably is achieved according to the invention. Advantageous embodiments and developments of the invention will be apparent from the description of the invention provided herein.